Researchers at the University of Kentucky have a better understanding of how extracellular vesicles are regulated by oxidative stress and how these vesicles propagate oxidative stress and can damage neurons. Extracellular vesicles are nanoparticles released by all types of cells that help carry information between cells.
The study, titled “Ceramide-mediated orchestration of the oxidative stress response through small filopodia-derived extracellular vesicles,” was recently published in the journal Journal of extracellular vesiclesthe leading journal for extracellular vesicle research.
“This study lays the foundation for understanding what happens during the exchange of extracellular vesicles between different cell types, and then for understanding the importance of these processes in neurodegenerative diseases like Alzheimer’s disease,” said Erhard Bieberich, Ph.D., professor at the University of California, Berkeley. Department of Physiology in the UK College of Medicine.
Bieberich is the principal investigator on a series of grants from the National Institute on Aging (NIA) of the National Institutes of Health (NIH) and the United States Department of Veterans Affairs who funded the study.
Bieberich’s research team focused on oxidative stress, an excess of oxygen radicals in the body. This excess causes damage to cells and tissues. Other studies have shown that this phenomenon plays a role in many chronic and degenerative diseases.
The researchers studied HeLa cellsso-called “immortal” cells because of their unique ability to grow and divide continuously in the laboratory. When exposed to hydrogen peroxide, these cells form filopodia (finger-like projections of cell membranes) and secrete extracellular vesicles (tiny structures released from cell membranes).
“In our study, we investigated the function of ceramide, which is a type of fatty compound, in filopodia formation and extracellular vesicle secretion, both induced by oxidative stress,” Bieberich said.
“Using a novel metabolic labeling technique, we discovered that these two processes are controlled by two enzymes that generate ceramide at the plasma membrane,” said Zainuddin Quadri, first author of the study and a senior research associate in the Department of Physiology. “This leads to the release of small ceramide-rich extracellular vesicles from the filopodia, which then target mitochondria and cause cell death.”
“Previous research has focused on oxidative stress caused by the accumulation of amyloid in plaques or other proteins in neurons,” Bieberich said. “We have discovered a new mechanism by which oxidative stress can propagate through extracellular vesicles, which can propagate cell death even if the neurons themselves are not directly exposed to harmful proteins like amyloid.”
The two researchers said the induction of cell death was observed particularly in neuronal cells, but plan to study the process in more detail in different cell types.
Their results suggest that targeting the interaction between the two enzymes could be a potential therapeutic target to prevent oxidative stress-induced cell death.
This research was made possible by the collaboration of two lipid biologists, Stefanka Spassieva, Ph.D., and Mariana Nikolova-Karakashian, Ph.D., from the Department of Physiology. They are also co-authors of the publication.
The research presented in this publication was supported by funding from the National Institute on Aging of the National Institutes of Health under grant numbers R01AG064234, RF1AG078338, and R21AG078601. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
This article is based upon work supported by the Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development. The views expressed in this article are those of the authors and do not necessarily reflect the position or policy of the Department of Veterans Affairs or the United States Government.
/Public dissemination. This content from the original organization/authors may be of a timely nature and edited for clarity, style, and length. Mirage.News takes no institutional position or bias, and all views, positions, and conclusions expressed herein are solely those of the author(s). See the full story here.